PXD073479

PXD073479 is an original dataset announced via ProteomeXchange.

Title	FAF2 enhances unfoldase activity of mammalian p97-UFD1-NPL4 complex enabling rational design of p97
Description	To address how adaptor proteins impact human p97 activity, we here employ in vitro reconstitution and a focused biochemical screen to identify adaptors that enhance unfoldase activity of human p97 in the presence of UFD1-NPL4. Of the adaptors tested, Fas-associated factor 2 (FAF2/UBXD8), a UBX domain adaptor protein, shows the strongest effect on unfolding by p97-UFD1-NPL4 complex. Through biochemical and structural analysis, we define the molecular features that underpin FAF2-mediated stimulation. Based on these insights, we employ computational protein design to engineer de novo mini-proteins that mimic FAF2 function within novel protein scaffolds to potently activate p97. Our work reveals how the unfoldase activity of p97 can be enhanced by additional adaptors, an adaptive feature we believe is important to unfold misfolded proteins, extract proteins from the membrane and tightly bound multiprotein complexes.
HostingRepository	PRIDE
AnnounceDate	2026-07-28
AnnouncementXML	Submission_2026-07-28_04:31:15.185.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Glenn Masson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	SELECT SERIES Cyclic IMS

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-23 13:44:04	ID requested
⏵ 1	2026-07-28 04:31:15	announced

Dataset with its publication pending

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: FAF2, HDX-MS,p97

Glenn Masson
contact affiliation	School of Medicine, University of Dundee
contact email	gmasson001@dundee.ac.uk
lab head
Glenn Masson
contact affiliation	University of Dundee
contact email	gmasson001@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073479
     1. Label: PRIDE project
     2. Name: FAF2 enhances unfoldase activity of mammalian p97-UFD1-NPL4 complex enabling rational design of p97